BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site

Abstract

Oncogenic BRAF mutations are more frequent in cutaneous melanoma occurring at sites with little or moderate sun-induced damage than at sites with severe cumulative solar ultraviolet (UV) damage. We studied cutaneous melanomas from geographic regions with different levels of ambient UV radiation to delineate the relative effects of cumulative UV damage, age, and anatomic site on the frequency of BRAF mutations. We show that BRAF-mutated melanomas occur in a younger age group on skin without marked solar elastosis and less frequently affect the head and neck area, compared to melanomas without BRAF mutations. The findings indicate that BRAF-mutated melanomas arise early in life at low cumulative UV doses, whereas melanomas without BRAF mutations require accumulation of high UV doses over time. The effect of anatomic site on the mutation spectrum further suggests regional differences among cutaneous melanocytes.

Figure 1

a) Result of classification and regression tree (CART) analysis of 409 melanomas from Europe and North America. b) 118 melanomas from Australia. The % indicates the percentage of BRAF-mutated melanomas in each subgroup. The boxes represent sub-groups of the data; the size of the boxes represent the sample size of the sub-groups; the location of the boxes is according to the % BRAF-mutated melanomas in the sub-groups; final sub-groups were represented by grey-highlighted boxes.